Abstract

In this fiscal year we have made three major discoveries in the survival of neurons. (1) The sigma-1 receptor may play a role in the population control of neurons and glia by regulating the signaling of the transcription factor Nrf2; (2) The Zinc finger protein (Znf179) is a neuroprotective molecule and is a downstream effector of sigma-1 receptor. We found that Znf179 is upregulated when brains are under ischemic stroke. Interestingly, the reactive oxygen species resulting from brain injury can cause Znf179 to enter the nucleus to interact with a transcription factor Sp1 that in turn increases the gene expression of Znf179. Thus the Znf179 can be increased upon brain injury through an autoregulatory mechanism. Additionally, we found that the sigma-1 receptor agonist DHEAS can increase the level of Znf179 that leads to protection against ischemic brain damage.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIADA000549-09
Application #
9553206
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Tsai, Shang-Yi Anne; Su, Tsung-Ping (2017) Sigma-1 Receptors Fine-Tune the Neuronal Networks. Adv Exp Med Biol 964:79-83
Weng, Tzu-Yu; Hung, Denise T; Su, Tsung-Ping et al. (2017) Loss of Sigma-1 Receptor Chaperone Promotes Astrocytosis and Enhances the Nrf2 Antioxidant Defense. Oxid Med Cell Longev 2017:4582135
Chuang, Jian-Ying; Kao, Tzu-Jen; Lin, Shu-Hui et al. (2017) Specificity protein 1-zinc finger protein 179 pathway is involved in the attenuation of oxidative stress following brain injury. Redox Biol 11:135-143
Williams, Abasha; Hayashi, Teruo; Wolozny, Daniel et al. (2016) The non-apoptotic action of Bcl-xL: regulating Ca(2+) signaling and bioenergetics at the ER-mitochondrion interface. J Bioenerg Biomembr 48:211-25
Su, Tzu-Chieh; Lin, Shu-Hui; Lee, Pin-Tse et al. (2016) The sigma-1 receptor-zinc finger protein 179 pathway protects against hydrogen peroxide-induced cell injury. Neuropharmacology 105:1-9
Ciesielski, Jenna; Su, Tsung-Ping; Tsai, Shang-Yi (2016) Myristic acid hitchhiking on sigma-1 receptor to fend off neurodegeneration. Receptors Clin Investig 3:
Tsai, Shang-Yi A; Pokrass, Michael J; Klauer, Neal R et al. (2015) Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid. Proc Natl Acad Sci U S A 112:6742-7
Lewis, Abasha; Hayashi, Teruo; Su, Tsung-Ping et al. (2014) Bcl-2 family in inter-organelle modulation of calcium signaling; roles in bioenergetics and cell survival. J Bioenerg Biomembr 46:1-15
Kaneko, Yuji; Tajiri, Naoki; Su, Tsung-Ping et al. (2012) Combination treatment of hypothermia and mesenchymal stromal cells amplifies neuroprotection in primary rat neurons exposed to hypoxic-ischemic-like injury in vitro: role of the opioid system. PLoS One 7:e47583
Fujimoto, Michiko; Hayashi, Teruo; Su, Tsung-Ping (2012) The role of cholesterol in the association of endoplasmic reticulum membranes with mitochondria. Biochem Biophys Res Commun 417:635-9

Showing the most recent 10 out of 18 publications